Continuous outcomes were compared using MannCWhitney U test or linear regression. workers (HCWs), we studied the association between seasonal HCoV (OC43, HKU1, 229E and NL63) nucleocapsid protein IgG and SARS-CoV-2 infection during the first pandemic wave in the Netherlands (March 2020 C June 2020), by 4-weekly serum sampling. HCW with HCoV-OC43 antibody levels in the highest quartile, were less likely to become SARS-CoV-2 seropositive when compared with those with lower levels (6/32, 18.8%, versus 42/97, 43.3%, respectively: p?= 0.019; HR 0.37, 95% CI 0.16C0.88). We found no significant SR-12813 association with HCoV-OC43 spike protein IgG, or with antibodies against other HCoVs. Our results indicate that the high levels of HCoV-OC43-nucleocapsid antibodies, as an indicator of a recent infection, are associated with protection against SARS-CoV-2 infection; this supports and informs efforts to develop pancoronavirus vaccines. Subject areas: Molecular physiology, Immunology, Virology Graphical abstract Open in a separate window Highlights ? High OC43 anti-nucleocapsid IgG suggests a recent infection with human coronavirus OC43 ? Persons with high OC43 anti-nucleocapsid IgG are less likely to contract SARS-CoV-2 Molecular physiology; Immunology; Virology Introduction The ongoing SARS-CoV-2 pandemic is characterized by a large individual variability in the risk of contracting infection and subsequent disease severity (Hu et?al., 2021; Liu, 2021). Vaccination efforts have been successful in protecting individuals against symptomatic infection and especially severe disease, but sustaining long term protection remains a problem, especially in the light of emerging immune-evasive variants (Hoffmann et?al., 2022; Lin et?al., 2022b). The potential of cross-protection against SARS-CoV-2 infection elicited by previous infections with seasonal human coronaviruses (HCoVs) is therefore of great interest, but studies have yielded conflicting results (Anderson et?al., 2021; Dugas et?al., 2021; Ladner et?al., 2021; Lin et?al., 2022a; Ortega et?al., 2021; Sagar et?al., 2021; Song et?al., 2021). In this study we prospectively followed a cohort of health care workers (HCW) with different levels of exposure to SARS-CoV-2, and assessed the association between levels of pre-existing HCoV antibodies, incidence of SARS-CoV-2 infection over time, disease severity and SARS-CoV-2 neutralizing immunity in those that became infected. Higher baseline HCoV-OC43 nucleocapsid protein IgG concentrations are associated with markedly lower incidence of SARS-CoV-2 infection. Future interventions against coronaviruses could take advantage of this cross-protective effect, e.g., by incorporating conserved coronavirus antigens to generate pancoronavirus vaccines. Results High HCoV-OC43 nucleocapsid IgG levels are associated with lower SARS-CoV-2 incidence Serum IgG antibodies against the C-terminal domain of nucleocapsid protein (NCt) of seasonal HCoVs OC43, HKU1, 229E, NL63, and total Ig antibodies against S1-RBD of SARS-CoV-2, were measured every 4?weeks during the first COVID-19 wave in the Netherlands (March 2020 – June 2020) in a cohort of 150 HCW (see Table?1 for characteristics). IgG concentrations against all seasonal HCoVs remained relatively stable during the study period (Figures?1AC1H). We hypothesized that if there was any cross-protection by HCoV immunity, this would most likely affect HCW with the most recent seasonal HCoV infection, and therefore those with the highest IgG levels. Plotting the HCoV anti-NCt IgG levels against the probability of contracting a SARS-CoV-2 infection revealed that these potential associations were likely non-linear (Figures?2AC2D). We therefore used baseline seasonal HCoV antibody concentration as SR-12813 a dichotomous determinant throughout the study (highest Rabbit Polyclonal to PXMP2 quartile versus lower concentrations; see Tables S1 and S2). During follow-up, 18.8% (6/32) of participants with anti-NCt SR-12813 IgG concentrations against HCoV-OC43 in the highest quartile at baseline became SARS-CoV-2 seropositive, compared with 43.3% (42/97) of those with lower antibody concentrations (p?= 0.019; HR 0.37, 95% CI 0.16C0.88; Figure?3A and Table?2). To correct for possible confounding SR-12813 effects by work-related bedside exposure to COVID-19 patients, we performed a multivariable Cox regression analysis, which showed a consistent result (HR 0.41, 95% CI SR-12813 0.18C0.97, Table?2). We did not find an association.
